AB0470 EFFECT OF TOFACITINIB IN MODULATING PLATELET FUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: D. Mauro, D. Iacono, I. Pantano, M. Raimondi, M. L. Marchesano, F. Riccio, A. Pellegrino, V. Liakouli, F. Ciccia
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Recent data suggested an association between Tofacitinib treatment and increased cardiovascular events in patients with Rheumatoid arthritis. Janus Kinase inhibitors (JAKi), specifically JAK3, have been demonstrated to be one of the regulators of platelet function. Treating platelets with thrombin induces tyrosine phosphorylation of the JAK3 target substrates STAT1 and STAT3, and JAK3 deficiency in mice reduces platelet aggregation and improves event-free survival in thromboplastin-induced thromboembolism. <h3>Objectives</h3> This study aimed to study the ability of the JAK1/JAK3 inhibitor, Tofacitinib, to influence platelet activity in patients with Rheumatoid Arthritis. <h3>Methods</h3> We enrolled patients with a diagnosis of RA according to the ACR/EULAR 2010 ACR/EULAR criteria. Peripheral blood was obtained from RA patients at the baseline and after 1, 3 and 6 months of Tofacitinib therapy. Platelet aggregation assay was performed by optical aggregometry stimulated with the thromboxane A<sub>2</sub> receptor in RA patients and controls. The aggregation test was performed before starting the therapy with Tofacitinib and after one month, three months and six months. <h3>Results</h3> 25 RA patients treated with Tofacitinib were recruited, 86% female and 14 % male, with a mean age of 56.5 years (SD 9.7 yrs.), mean disease duration of 16.3 years, mean ESR 28.2 mm, mean CRP 0.9 mg/dl, mean SDAI 18.2 and mean prednisone equivalent dose 3.75 mg/die. 78% of the patients were positive for Rheumatoid factor and 57.1% for ACPA. Looking at the classical risk factors, 35.7 had hypertension, 21.4% had hypercholesterolemia, 16.2% had diabetes, and 14.2% were smokers.; only one patient had a previous cardiovascular event. The platelet aggregation was not influenced by Tofacitinib treatment at any time points (T1, T3 and T6) at any Thromboxane dose (5uM and 20 uM), furthermore did not differ from patients and controls basally (64%, SD 15.84% vs 62%, SD 10.5%). <h3>Conclusion</h3> In conclusion, Tofacitinib does not increase platelet aggregation in patients treated for Rheumatoid Arthritis. <h3>References</h3> [1]Lu, W.-J., Lin, K.-C., Huang, S.-Y., Thomas, P. A., Wu, Y.-H., Wu, H.-C., Lin, K.-H., &amp; Sheu, J.-R. (2014). Role of a Janus kinase 2-dependent signaling pathway in platelet activation. <i>Thrombosis Research</i>, <i>133</i>(6), 1088–1096. [2]Parra-Izquierdo, I., Melrose, A. R., Pang, J., Lakshmanan, H. H. S., Reitsma, S. E., Vavilapalli, S. H., Larson, M. K., Shatzel, J. J., McCarty, O. J. T., &amp; Aslan, J. E. (2022). Janus kinase inhibitors ruxolitinib and baricitinib impair glycoprotein-VI mediated platelet function. <i>Platelets</i>, <i>33</i>(3), 404–415. <h3>Acknowledgements</h3> Research was supported by an unrestricted grant by Pfizer. <h3>Disclosure of Interests</h3> Daniele Mauro Grant/research support from: Research was supported by an unrestricted grant by Pfizer, Daniela Iacono Grant/research support from: Research was supported by an unrestricted grant by Pfizer, Ilenia Pantano Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Maura Raimondi Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Maria Laura Marchesano Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Flavia Riccio Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Anna Pellegrino Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Vasiliki Liakouli Grant/research support from: Some research was supported by an unrestricted grant by Pfizer, Francesco Ciccia Grant/research support from: Some research was supported by an unrestricted grant by Pfizer.